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Abstract

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures1,2. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging3,4,5 offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal–oxide–semiconductor (CMOS) processing-compatible low-impedance TiN6 sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.

References

Bargmann, C.et al.BRAIN 2025: a Scientific Vision; Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Working Group Report to the Advisory Committee to the Director, NIH. Available at: http://www.nih.gov/science/brain/2025/ (2014)

Acknowledgements

We thank the support of the charities that fully funded this work: Howard Hughes Medical Institute’s Janelia Research Campus, Allen Institute for Brain Science, Gatsby Charitable Foundation (grant GAT3353), and the Wellcome Trust (grant 100154). We thank S. Caddick for early and continued enthusiastic support of the project. We thank G. Buzsáki for advice and D. Rinberg for early discussions and advocacy. C.M., S.L.G. and C.A.A. would like to thank NSG portal personnel for offering core-hour access to the San Diego Supercomputer Center, troubleshooting and support. The Allen Institute for Brain Science wishes to thank the enduring support of our founders, Paul G. Allen and Jody Allen, without whom this work could not have been accomplished. J.C., C.A. and V.B. were funded by NERF. Experiments and software development in the laboratory of M.C. and K.D.H. were supported by the Wellcome Trust (grants 095668 and 095669). M.C. holds the GlaxoSmithKline/Fight for Sight Chair in Visual Neuroscience. N.A.S. was supported by postdoctoral fellowships from the Human Frontier Science Program and the Marie Curie Actions of the EU.

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Editorial Summary

High-density neural activity probe

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions. Existing technologies reliably measure activity from a relatively small number of neurons with high spatial and temporal resolution, or from a large volume of neurons with low resolution. Timothy Harris and colleagues describe the design, fabrication and performance of Neuropixels, a silicon probe that can measure well-isolated neural activity from hundreds of neurons. They integrated these probes into a lightweight system that could record activity simultaneously and with high fidelity from hundreds of neurons in awake and freely moving rodents.